The ABO(H) blood group antigens appear to become dedifferentiated or are incompletely developed in many cases of cancer, particularly those characterized by marked anaplasia or metastases. Such losses could reflect deficiencies of the corresponding blood group transferase enzymes which are normally present as gene products. In malignancies characterized by deficient blood group activity it seems appropriate to determine whether such losses are due primarily to blood group transferase enzyme deficiency, or, alternatively to deficient acceptor molecules which cannot accept a specific sugar when its corresponding enzyme is normally available. It is also possible that some cancers produce both conditions which might be local or generalized depending on the nature and extent of the disease. It is proposed to study this problem prospectively as follows: tissue extract will be prepared from carcinomas mainly those of gastrointestinal origin, and from other malignancies such as acute leukemia. By means of hemagglutinin inhibition and agglutinin absorption, we will determine patterns of altered ABO(H) and carbohydrate specific lectin activity which might be characterized enough to be of potential value in cancer diagnosis or immunology therapy. Parallel studies will be carried out on smears and histologic sections of tissue using agglutination and fluorescent labelling methods. Comparisons will be made with corresponding normal tissues and organs. In cases where blood group deficiencies are demonstrable, specific blood group transferase enzymes will be searched for in tissue extracts and serum to determine whether they are local and/or general reflections of such changes in a blood group antigen. Blood group deficient cells from cancer patients will also be examined in the presence of normal amounts of transferase enzymes corresponding to the patients normal erythrocytic group to determine the functional status of the acceptor molecules on these cells. The possible usefulness of such tests in cancer diagnosis will be determined in serial patient investigation.